The Impact of Revascularization Strategy on Clinical Failure, Hemodynamic Failure and Chronic Limb Threatening Ischemia Symptoms in the BEST-CLI Trial.

OBJECTIVES: Sustained clinical and hemodynamic benefit following revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI following endovascular (ENDO) vs bypass (OPEN) revascularization in the BEST-CLI trial. METHODS: As planned secondary analyses of the BEST-CLI trial, we examined the rates of A) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); B) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to initially increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); C) time to resolution of presenting CLTI symptoms; and D) incidence of recurrent CLTI. Time-to-event analyses were by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N=1434; cohort 2: lacking suitable SSGSV, N= 396) and multivariate stratified Cox regression models were created. RESULTS: In cohort 1, there was a significant difference in time to clinical failure (log-rank p<0.001), hemodynamic failure (log-rank p<0.001), and resolution of presenting symptoms (log-rank p=0.009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank p=0.006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with significantly lower risk of clinical and hemodynamic failure in both cohorts, and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end stage renal disease (ESRD), prior revascularization, smoking, diabetes, age>80, WIfI stage, tissue loss, infrapopliteal disease). Factors independently associated with clinical failure included age>80 in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. CONCLUSIONS: Durable clinical and hemodynamic benefit following revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

The Use of Clot Strength as a Predictor of Thrombosis in Peripheral Artery Disease.

OBJECTIVES: Graft/stent thrombosis is the leading cause of amputation in patients over 60, and while dual antiplatelet therapy is the standard of care, there is a significant variability in platelet response and limited guidance on measuring effectiveness. Thromboelastography with platelet mapping (TEG-PM) can objectively detail an individual's coagulation profile, namely the strength of the clot and its response to antiplatelet medication. Although TEG-PM has been used for predicting postoperative bleeding and assessing platelet dysfunction in TBI, its application in thrombosis diseases such as peripheral artery disease (PAD) remains unexplored. The aim of this observational study was to determine if objective measures of clot strength could predict a high clinical risk of thrombosis. METHODS: Patients > 60 years with peripheral artery disease (PAD) undergoing revascularization were prospectively evaluated from 2021-2023. They were clinically followed for one year to detect any thrombotic events. TEG-PM was used to objectively evaluate coagulation profiles in patients at 1, 3, 6, and 9 months. These follow-up periods were chosen based on studies showing that 1-3 month intervals in the first year after lower extremity revascularization (LER) optimize therapy and risk control. The TEG-PM data preceding a thrombotic/stenotic event in patients with thrombosis was compared to the last known well TEG-PM event in those without a thrombotic/stenotic event. We stratified the groups based on the occurrence of thrombosis/stenotic events. Descriptive statistics were applied to characterize each group and a chi-square test was conducted to assess the variance between both groups. An unpaired t-test was ran to identify differences in platelet function. ROC analysis was performed to determine the optimal TEG-PM cutoff for predicting a higher risk of thrombosis. RESULTS: One hundred and fifty-eight patients were analyzed, from whom 28 (17.7%) experienced a thrombotic event. The thrombosis cohort exhibited significantly greater MAADP, MAFibrin, and MAThrombin [50.2 vs. 40.0, p<0.05], [18.19 vs. 14.64, p<0.05] and [63.8 vs. 58.5, p<0.05] respectively indicative of greater clot strength. By ROC analysis, the optimal predictor cutoff for MAADP, indicating a higher risk of thrombosis, was >42mm [p<0.05] with 82% sensitivity and 50% specificity. CONCLUSIONS: An increase in clot strength was found to be predictive of thrombosis/stenosis within 30 days. Using a MAADP cutoff greater than 42mm might serve as an alternative approach to tailor the use of antiplatelet medication, potentially reducing the risk of thrombosis.

Prediction of Peripheral Artery Disease Prognosis Using Clinical and Inflammatory Biomarker Data.

Purpose: Inflammatory biomarkers associated with peripheral artery disease (PAD) have been examined separately; however, an algorithm that includes a panel of inflammatory proteins to inform prognosis of PAD could improve predictive accuracy. We developed predictive models for 2-year PAD-related major adverse limb events (MALE) using clinical/inflammatory biomarker data. Methods: We conducted a prognostic study using 2 phases (discovery/validation models). The discovery cohort included 100 PAD patients that were propensity-score matched to 100 non-PAD patients. The validation cohort included 365 patients with PAD and 144 patients without PAD (non-matched). Plasma concentrations of 29 inflammatory proteins were determined at recruitment and the cohorts were followed for 2 years. The outcome of interest was 2-year MALE (composite of major amputation, vascular intervention, or acute limb ischemia). A random forest model was trained with 10-fold cross-validation to predict 2-year MALE using the following input features: 1) clinical characteristics, 2) inflammatory biomarkers that were expressed differentially in PAD vs non-PAD patients, and 3) clinical characteristics and inflammatory biomarkers. Results: The model discovery cohort was well-matched on age, sex, and comorbidities. Of the 29 proteins tested, 5 were elevated in PAD vs non-PAD patients (MMP-7, MMP-10, IL-6, CCL2/MCP-1, and TFPI). For prognosis of 2-year MALE on the validation cohort, our model achieved AUROC 0.63 using clinical features alone and adding inflammatory biomarker levels improved performance to AUROC 0.84. Conclusion: Using clinical characteristics and inflammatory biomarker data, we developed an accurate predictive model for PAD prognosis.

Inflammatory biomarkers associated with peripheral artery disease (PAD) have been examined separately; however, an algorithm that includes an inflammatory protein panel to inform prognosis of PAD may improve predictive accuracy. We developed predictive models for 2-year major adverse limb events (MALE) using clinical characteristics (demographics, comorbidities, and medications) and a panel of 5 PAD-specific inflammatory biomarkers (MMP-7, MMP-10, IL-6, CCL2/MCP-1, and TFPI) that achieved excellent performance on an independent validation cohort (AUROC 0.84). The models developed through this study may support PAD risk-stratification and targeted management strategies.

Addressing Psychosocial Care Needs in Women with Peripheral Artery Disease.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is a growing global epidemic. Women with PAD are at elevated risk of experiencing psychosocial stressors that influence the diagnosis, management, and course of their illness due to unique sex- and gender-based factors. RECENT FINDINGS: We review existing evidence for increased psychosocial risk in women with PAD with a focus on mood disorders, chronic stress, pain experiences, substance use disorders, health behaviors and illness perceptions, and healthcare access. We discuss how these factors exacerbate PAD symptomatology and lead to adverse outcomes. Existing gaps in women's vascular care are reviewed and potential solutions to bridge these gaps through psychosocial care integration are proposed. Current care paradigms for women's vascular care do not adequately screen for and address psychosocial comorbidities. Clinician education, integration of evidence-based psychological care strategies, implementation of workflows for the management of individuals with PAD and mental health comorbidities, reform to reimbursement structures, and further advocacy are needed in this space. This review provides a construct for integrated behavioral health care for women with PAD and advocates for further integration of care.

Variations of VEGFR2 Chemical Space: Stimulator and Inhibitory Peptides.

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR type 2 angiogenesis and vascular morphogenesis as the tyrosine kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between Vascular Endothelial Growth Factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

Risk Factors for Unplanned Higher-Level Re-Amputation and Mortality after Lower Extremity Amputation in Chronic Limb-Threatening Ischemia.

Background: The factors associated with unplanned higher-level re-amputation (UHRA) and one-year mortality among patients with chronic limb-threatening ischemia (CLTI) after lower extremity amputation are poorly understood. Methods: This was a single-center retrospective study of patients who underwent amputations for CLTI between 2014 and 2017. Unadjusted bivariate analyses and adjusted odds ratios (AOR) from logistic regression models were used to assess associations between pre-amputation risk factors and outcomes (UHRA and one-year mortality). Results: We obtained data on 203 amputations from 182 patients (median age 65 years [interquartile range (IQR) 57, 75]; 70.7% males), including 118 (58.1%) toe, 20 (9.9%) transmetatarsal (TMA), 37 (18.2%) below-knee (BKA), and 28 (13.8%) amputations at or above the knee. Median follow-up was 285 days (IQR 62, 1348). Thirty-six limbs (17.7%) had a UHRA, and the majority of these (72.2%) were following index forefoot amputations. Risk factors for UHRA included non-ambulatory status (AOR 6.74, 95% confidence interval (CI) 1.74-26.18; p < 0.10) and toe pressure < 30 mm Hg (AOR 4.89, 95% CI 1.52-15.78; p < 0.01). One-year mortality was 17.2% (n = 32), and risk factors included coronary artery disease (AOR 3.93, 95% CI 1.56-9.87; p < 0.05), congestive heart failure (AOR 4.90, 95% CI 1.96-12.29; p = 0.001), end-stage renal disease (AOR 7.54, 95% CI 3.10-18.34; p < 0.001), and non-independent ambulation (AOR 4.31, 95% CI 1.20-15.49; p = 0.03). Male sex was associated with a reduced odds of death at 1 year (AOR 0.37, 95% CI 0.15-0.89; p < 0.05). UHRA was not associated with one-year mortality. Conclusions: Rates of UHRA after toe amputations and TMA are high despite revascularization and one-year mortality is high among patients with CLTI requiring amputation.

Mortality in Amputees with Peripheral Artery Disease during the Post-COVID Era: A Three-Year Analysis.

BACKGROUND: Patients with peripheral artery disease (PAD) have 40-70% higher three-year mortality after lower limb amputation compared to non-amputees. In this study, we examined the consequences of delayed treatment for patients with PAD during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study employed a retrospective single-centre cohort design at a large tertiary care hospital. We compared amputees with PAD during the initial COVID-19 outbreak period in 2020 with a control group of amputees from 2019 after a three-year follow-up. RESULTS: In total, 134 amputees with PAD were included due to unsuccessful revascularization (n = 84 in 2020 vs. n = 50 in 2019). Patients in 2020 were significantly younger than those in 2019 (p = 0.01) and mostly admitted with advanced stages of PAD (p < 0.03). The proportion of major limb amputations increased significantly in 2020 (p = 0.03). Non-COVID-19-related deaths among patients in 2020 were more than twice as many as those in 2019, and long-term mortality in 2020 was 49% compared to 39% in 2019 (p = 0.04). Diabetes and renal insufficiency had a significantly negative impact on the survival of amputees with PAD (p < 0.01). CONCLUSIONS: Delayed treatment in patients with PAD leads to high long-term mortality risk after amputation, especially in PAD patients with diabetes and renal insufficiency. Therefore, in future pandemics, continuously monitoring patients with PAD will be crucial to prevent delayed treatment and severe short-term and long-term consequences.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Impact of the Coexisting Coronary Artery Disease on Five-Year Outcomes in Lower Extremity Artery Disease Patients Without Chronic Limb-Threatening Ischemia.

Coronary artery disease (CAD) is often noted in patients with lower-extremity artery disease (LEAD). However, the effects of CAD on patients with LEAD have not been clearly investigated. In this study, to investigate the effect of CAD on patients with LEAD without chronic limb-threatening ischemia (CLTI), we compared the five-year clinical outcomes of patients with and without CAD. Between 2014 and 2017, 246 patients with symptomatic LEAD without CLTI underwent endovascular treatment. Patients with a history of CAD revascularization or CAD defined by CAD studies were divided into CAD groups, and others were non-CAD groups. After excluding ineligible patients, propensity matching produced 40 patients in each group, and clinical outcomes were compared between the groups. Using five years of Kaplan-Meier analysis between the CAD and non-CAD groups, no significant differences were observed in survival (90.0% vs 92.5%, p=0.693), freedom from cardiovascular events (42.5% vs 57.5%, p=0.110), freedom from LEAD revascularization (67.5% vs 67.5%, p=0.940), and freedom from CLTI (100% vs. 95.0%, p=0.148). However, significant differences were observed in freedom from CAD revascularization (67.5% vs 97.5%, p<0.001) and freedom from symptomatic CAD (85.0% vs 97.5%, p=0.048). Our results suggest that in patients with LEAD without CLTI, CAD caused increased CAD revascularization and symptomatic CAD. However, CAD did not affect survival, cardiovascular events, LEAD revascularization, or CLTI in such patients. When CAD was observed in patients with LEAD without CLTI, more frequent follow-up of CAD may improve the long-term clinical outcomes of such patients.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20-54 and over 55 years: insights from the Global Burden of Disease Study 2019.

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Applications of SPECT and PET Imaging for the Physiological Evaluation of Lower Extremity Peripheral Artery Disease.

Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD involves lifestyle and symptom management, statin and antiplatelet therapy, and/or surgical interventions to improve quality of life with varying efficacy. PAD affects approximately 5 to 6 percent of the global population, with this global burden continuing to increase. Despite the increase in disease prevalence, no gold standard functional diagnostic tool has been established for enabling early detection of the disease, appropriate medical management, and prediction of adverse outcomes for PAD patients. The visualization and quantification of the physiological consequences of PAD are possible by way of nuclear imaging: specifically, via scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging. These non-invasive modalities, when combined with targeted radionuclides, possess utility for detecting functional perfusion deficits and provide unique insight into muscle tissue- and vascular-level characteristics of PAD patients. This review discusses the past, present, and emerging applications of hybrid nuclear imaging modalities in the evaluation and monitoring of patients with PAD.

An unfavorable dietary pattern is associated with symptomatic peripheral artery disease.

BACKGROUND AND AIMS: Diet has an essential role in primary and secondary cardiovascular prevention by modulating various cardiovascular risk factors. The need to have easily useable tools seems essential to facilitate the daily practice of clinicians in order to propose the most optimal management of their patients' diet. The aim of this study was to compare the diet assessed with a simple food frequency questionnaire (FFQ) between patients with symptomatic peripheral artery disease (PAD) and healthy subjects. MATERIALS AND RESULTS: In this ancillary study (ELECTRO-PAD study), we included symptomatic PAD patients and healthy participants. All participants filled a FFQ previously validated called Cardiovascular-Dietary-Questionnaire 2 (CDQ-2). CDQ-2 allows the calculation of different scores: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score. The higher the score, the better the diet. We compared the different scores between PAD patients and healthy participants. We included 37 PAD patients and 40 healthy subjects. Mean global score was significantly lower in PAD patients compared to the healthy participants (5.35 ± 7.65 vs 10.60 ± 5.81; p = 0.0011). Similarly, the sub-scores concerning unsaturated fatty acids and fruits-vegetables were significantly lower in PAD patients (p < 0.010). Only the sub-score concerning saturated fatty acids was not significantly different (p = 0.8803) between PAD patients and healthy participants. CONCLUSION: CDQ-2 highlights that PAD patients have an unfavorable diet compared with healthy participants. CDQ-2 is a tool of interest to help the clinicians for dietary advice of PAD patients.

Introduction of novel intravascular ultrasound preceding with angled guiding catheter (I-PAD) technique to treat chronic total occlusions in peripheral artery disease.

BACKGROUND: The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. CASE PRESENTATION: A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. CONCLUSIONS: The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Importance of Using Angiography for the Early Detection of Chronic Limb Ischemia in Diabetic Foot Wounds.

Peripheral artery disease (PAD) affects millions of people worldwide, presenting with varying symptom severity, including chronic total occlusion of arteries, and occasionally, limb amputation. There are various interventions, such as atherectomy and the use of drug-coated balloons and stents, which have been developed to revascularize affected ischemic regions. However, each interventional approach must be individualized due to a patient's unique underlying conditions. Comorbid conditions, especially diabetes, play a significant role in PAD, as poorly controlled diabetes can accelerate PAD progression. For this reason, an early and accurate diagnosis of PAD is crucial, especially when symptoms may present dissimilar to classic PAD symptoms, often leading to misdiagnosis. The presented cases highlight the tailored interventions to revascularize arteries in patients with diabetic foot wounds utilizing catheters, stents, guidewires, and balloons, made possible after early angiogram. These interventions have been promising in treating PAD patients, and highlight the need for early diagnosis and timely and customized interventions to prevent limb amputation and mitigate potential complications.

Association of endothelial function and lower extremity perfusion in peripheral artery disease.

Background: The current study aims to investigate the association between endothelial function and lower extremity perfusion in patients with peripheral artery disease (PAD). Patients and methods: In total 229 patients with PAD (Rutherford stage 0-3) were enrolled in the current study. Endothelial function was assessed by measuring flow-mediated dilation (FMD) and endothelial cell proliferation capacity (ECPC). Lower extremity perfusion was assessed by measuring oscillometry-based ankle brachial index (oABI) and pulse wave index (PWI). In addition, carotid intima-media-thickness (cIMT) was also measured as a surrogate marker for atherosclerosis. Correlations between FMD, ECPC, oABI, PWI, and cIMT were analysed using Pearson correlation coefficient. The relationship between the above variables and the severity of PAD was investigated using ordinal logistic regression analysis. Results: Correlation analysis showed that FMD negatively associated with PWI (r = -0.183, p = 0.005), ECPC positively associated with oABI (r = 0.162, p = 0.014), and oABI negatively associated with PWI (r = -0.264, p < 0.001). Ordinal logistic regression analysis showed that ECPC (ß = -0.009, p = 0.048), oABI (ß = -5.290, p < 0.001), and age (ß = -0.058, p = 0.002) negatively associated with the PAD Rutherford stages. In addition, PWI (ß = 0.006, p < 0.001), cIMT (ß = 18.363, p = 0.043) positively associated with the PAD Rutherford stages. Conclusions: Endothelial function significantly associates with lower extremity perfusion in patients with PAD, and both are related to the severity of PAD.

A Bibliometric Analysis on Adherence to Reporting Standards for Endovascular Treatment of Chronic Lower Extremity Peripheral Artery Disease.

OBJECTIVE: The treatment of chronic limb threatening ischemia (CLTI) involves a broad spectrum of therapies including many new and emerging techniques. To standardize results of studies examining this pathology and to allow critical analysis and comparison between studies, the Society for Vascular Surgery recommended reporting standard guidelines for the endovascular management of CLTI in 2016. Research studies that do not adhere to complete reporting standards are often more ambiguous in impact and external validity, leading to bias and misinformation that has potentially damaging effects on clinical decision making. We thus sought to examine adherence to, and factors associated with non-compliance with these recommended guidelines. METHODS: A literature database search was conducted to include all clinical trials, randomized controlled trials, and retrospective comparative studies written in English examining the endovascular treatment of PAD/CLTI from January 2020 to August 2022. Systematic reviews, case reports and meta-analysis were excluded. The manuscripts were reviewed for adherence with the SVS guidelines (overall and by guideline subcategories based on demographics, treatment methods and outcomes), and factors associated with this adherence were determined. This data was used to calculate descriptive and comparative statistics. RESULTS: 54 manuscripts were identified from this timeframe. On average, articles reviewed reported on 42.0% of the SVS reporting standards (range 25.0-65.2%, Fig 1) with 74.1% of articles (n=40) not adhering to at least 50.0% of the standards. Manuscripts most completely followed guidelines regarding "Patient Factors" and were least likely to demonstrate adherence to description of CLTI and study complications. Within the guideline subcategories, complete adherence to guidelines was not demonstrated in any manuscript in stent trials, disease outcome measures, technical outcome measures, patient factors and critical limb ischemia description, and complete adherence rates within the other subcategories was low (range 5.6-18.6%). Studies conducted within the United States and those with industry sponsorship were more likely to adhere to >50% of the reporting standards (p<0.05). Journal impact factor, year of publication, and number of authors had no correlation to the percent adherence to guidelines in specific categories or adherence overall. CONCLUSIONS: Adherence to reporting standard guidelines for endovascular treatment of lower extremity PAD specifically outlined by the SVS is suboptimal regardless of the quality of the journal the research is published in. Increasing adherence to reporting standards to provide a framework for comparison of studies across techniques used should be prioritized by authors, journal editors, and vascular societies.

Epidemiology and Burden of Peripheral Artery Disease in People With Type 2 Diabetes: A Systematic Literature Review.

Type 2 diabetes (T2D) and lower-extremity peripheral artery disease (PAD) are growing global health problems associated with considerable cardiovascular (CV) and limb-related morbidity and mortality, poor quality of life and high healthcare resource use and costs. Diabetes is a well-known risk factor for PAD, and the occurrence of PAD in people with T2D further increases the risk of long-term complications. As the available evidence is primarily focused on the overall PAD population, we undertook a systematic review to describe the burden of comorbid PAD in people with T2D. The MEDLINE, Embase and Cochrane Library databases were searched for studies including people with T2D and comorbid PAD published from 2012 to November 2021, with no restriction on PAD definition, study design or country. Hand searching of conference proceedings, reference lists of included publications and relevant identified reviews and global burden of disease reports complemented the searches. We identified 86 eligible studies, mostly observational and conducted in Asia and Europe, presenting data on the epidemiology (n = 62) and on the clinical (n = 29), humanistic (n = 12) and economic burden (n = 12) of PAD in people with T2D. The most common definition of PAD relied on ankle-brachial index values ≤ 0.9 (alone or with other parameters). Incidence and prevalence varied substantially across studies; nonetheless, four large multinational randomised controlled trials found that 12.5%-22% of people with T2D had comorbid PAD. The presence of PAD in people with T2D was a major cause of lower-limb and CV complications and of all-cause and CV mortality. Overall, PAD was associated with poor quality of life, and with substantial healthcare resource use and costs. To our knowledge, this systematic review provides the most comprehensive overview of the evidence on the burden of PAD in people with T2D to date. In this population, there is an urgent unmet need for disease-modifying agents to improve outcomes.

Hypertension in Patients With Peripheral Artery Disease: An Updated Literature Review.

Peripheral artery disease (PAD), a condition where there is reduced blood flow due to narrowing or blockage of the arteries of the peripheral vasculature, is an epidemic that currently affects eight million people in the United States alone and is a major risk equivalent to having active coronary artery disease (CAD). However, it is commonly underdiagnosed in the general population. Hypertension is a common cardiovascular condition characterized by elevated blood pressure levels. There are several mitigating risk factors that can reduce the risk of complications of PAD, with hypertension playing a major role. This literature review aims to explore the relationship between hypertension and PAD, including their shared risk factors, pathophysiological mechanisms, and management strategies. In addition, we will analyze how this impacts major cardiovascular outcomes, such as critical limb ischemia, vascular amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular-related death by examining relevant studies, current guidelines, and evidence. This literature review is intended to guide practitioners on ideal blood pressure parameters and evidence-based anti-hypertensives that provide overall cardiovascular benefit in both the primary care and hospital-based setting. By understanding the association between hypertension and PAD and the underlying pathophysiological mechanisms, healthcare professionals can improve diagnosis, treatment, and management strategies for affected individuals.

Effect of Peripheral Interventions in Patients with Peripheral Artery Disease Receiving Rivaroxaban and Aspirin: Analyses from the XATOA Registry.

OBJECTIVE: To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history. METHODS: XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariate analysis assessed the influence of patient characteristics on clinical outcomes. RESULTS: In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergent clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariate analyses showed that prior LER was predictive of limb events. CONCLUSION: This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials.

The Effect of Uric Acid and Albumin Ratio in Undergoing Lower Extremity Endovascular Interventions For Peripheral Arterial Disease Related Contrast Induced Nephropathy.

BACKROUND: Among patients undergoing percutaneous vascular intervention, contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality.Serum uric acid/albumin ratio (UAR) has emerged as a new marker associated with poor cardiovascular outcomes. We aimed to evaluate the relationship between UAR and CIN occurrence in patients treated for peripheral artery disease. METHODS: Patients underwent percutaneous intervention due to peripheral artery disease were enrolled. The primary endpoint was development of contrast related nephropathy. Patients were divided into two groups according to the CIN occurrence. RESULTS: 663 patients were enrolled and mean age was 62±10 years. After the intervention, 45 patients had CIN and 618 patients did not have CIN. Logistic regression analysis were performed to define the parameters of CIN. Male gender, diabetes, uric acid /albumin ratio, contrast volume, presence of coronary artery disease and CRP levels were found significant in univariate analysis. However, only UAR was found significant in multivariate analysis (OR 95% CI: 3.426 (1.059-11.079), (p=0.040)).Therefore ,it is the only independent predictor for occurrence of CIN. CONCLUSION: UAR is a reliable scoring system, which predicts CIN in such patient group. This score is not only cost-effective also simple, which can be easily applied into the clinical practice.